The expression and clinical value of LRP11, FUBP1 and TET1 in cervical cancer.

Cervical cancer is the second leading cause of cancer death among women worldwide. Identification of effective genes along with biological markers as targeting agents is very necessary for the diagnosis and treatment of this disease. Bioinformatics techniques along with genetic and molecular investigations have provided the possibility of studying different levels of information such as the genome, transcriptome, proteome, and metabolize with high depth and accuracy. The collection of these data provides comprehensive and valuable information about the investigated phenotypes, including complex diseases such as cancer. In this study, we examined three genes LRP11, FUBP1, and TET1 related to cervical cancer. The results of this study showed that the level of expression of these genes is high in lymph nodes and the thyroid and is less in the pancreas and liver. Also, the expression level of the FUBP1 gene is higher than that of LRP11, and the expression level of the LRP11 gene is higher than that of TET1. Regarding the structure and proteomics of the studied genes, it can be seen that due to the presence of more domains in the LRP11 and FUBP1 genes, these genes probably independently participate in various functions and have a wider range of activity than the TET1 gene. Also, the analysis of the stability of the examined genes showed that the stability of the FUBP1 gene is relatively higher than that of the TET1 gene, and this gene is also more stable than the LRP11 gene. Considering that these genes are effective key genes for the early detection of cervical cancer, it is hoped that they will be used as markers in the diagnosis and treatment of cervical cancer.

pH-Responsive Nanoparticles for Enhanced Antitumor Activity by High-Intensity Focused Ultrasound Therapy Combined with Sonodynamic Therapy.

BACKGROUND: Therapeutic ultrasound (US) has been extensively explored for its inherent high tissue-penetrating capability and on-demand irradiation without radioactive damage. Although high-intensity focused ultrasound (HIFU) is evolved as such an outstanding US-based approach, its insufficient therapeutic effect and the high-intensity induced potential damage to surrounding normal tissues hindered its development towards practical application. As opposed to high intensity ultrasound, sonodynamic therapy (SDT) is a low intensity US-based method which exhibits certain therapeutic effects against cancer via sonosensitizers-generated reactive oxygen species (ROS) overproduction. METHODS: Hematoporphyrin monomethyl ether (HMME) loaded CaCO3 nanoparticles (designated as Ca@H) were synthesized by a gas diffusion method. The pH-responsive performance, in vitro SDT, ex vivo HIFU therapy (HIFUT), photoacoustic (PA) imaging and in vivo HIFUT combined with SDT were investigated thoroughly. RESULTS: Ca@H NPs gradually decomposed in acid tumor microenvironment, produced CO2 and released HMME. Both CO2 and HMME enhanced photoacoustic (PA) imaging. The generated CO2 bubbles also enhanced HIFUT by inducing an enlarged ablation area. The tumor ablation efficiency (61.04%) was significantly improved with a combination of HIFU therapy and SDT. CONCLUSION: pH-responsive Ca@H NPs have been successfully constructed for PA imaging-guided/monitored HIFUT combined with SDT. With the assistance of pH-responsive Ca@H NPs, the combination of these two US-based therapies is expected to play a role in the treatment of non-invasive tumor in the future.

Mitochondria-targeted nanoplatforms for enhanced photodynamic therapy against hypoxia tumor.

BACKGROUND: Photodynamic therapy (PDT) is a promising therapeutic modality that can convert oxygen into cytotoxic reactive oxygen species (ROS) via photosensitizers to halt tumor growth. However, hypoxia and the unsatisfactory accumulation of photosensitizers in tumors severely diminish the therapeutic effect of PDT. In this study, a multistage nanoplatform is demonstrated to overcome these limitations by encapsulating photosensitizer IR780 and oxygen regulator 3-bromopyruvate (3BP) in poly (lactic-co-glycolic acid) (PLGA) nanocarriers. RESULTS: The as-synthesized nanoplatforms penetrated deeply into the interior region of tumors and preferentially remained in mitochondria due to the intrinsic characteristics of IR780. Meanwhile, 3BP could efficiently suppress oxygen consumption of tumor cells by inhibiting mitochondrial respiratory chain to further improve the generation of ROS. Furthermore, 3BP could abolish the excessive glycolytic capacity of tumor cells and lead to the collapse of ATP production, rendering tumor cells more susceptible to PDT. Successful tumor inhibition in animal models confirmed the therapeutic precision and efficiency. In addition, these nanoplatforms could act as fluorescence (FL) and photoacoustic (PA) imaging contrast agents, effectuating imaging-guided cancer treatment. CONCLUSIONS: This study provides an ideal strategy for cancer therapy by concurrent oxygen consumption reduction, oxygen-augmented PDT, energy supply reduction, mitochondria-targeted/deep-penetrated nanoplatforms and PA/FL dual-modal imaging guidance/monitoring. It is expected that such strategy will provide a promising alternative to maximize the performance of PDT in preclinical/clinical cancer treatment.

Quantitative Evaluation of Percutaneous Local Drug Perfusion Against Refractory Infantile Hemangioma via 3-D Power Doppler Angiography.

To assess the practicality of 3-D power Doppler angiography (3-D-CPA) for local drug perfusion dosage guidance of refractory infantile hemangioma (IH) treatment, 47 cases (48 lesions) of refractory IH were selected for local bleomycin infusion (once a month). Ultrasound was performed before treatment and 1 and 2 months after the first treatment. The 3-D volume (V) change of infantile hemangiomas and the ratio of bleomycin injection to 3-D V before treatment were calculated, and statistical analysis was performed. One month after percutaneous local drug perfusion, 37 participants (77.08%) exhibited significant improvement; controlled growth was observed on six lesions (12.5%); and treatment of the remaining 5 lesions (10.42%) failed to suppress growth. The calculated tolerable and effective dose of bleomycin for refractory IH was 0.34 ± 0.03 mL/cm3; the corresponding 3-D V decreased approximately 70.27 ± 6.27%. Three-dimensional CPA can provide abundant information on internal lesions. In particular, 3-D-CPA can quantitatively assess changes in lesion volume and guide the effective and rational use of interventional drugs.